The histone deacetylase inhibitor trichostatin A influences the development of Drosophila melanogaster

We examined the consequences of the deacetylase inhibitor trichostatin A (TSA) on the development of Drosophila melanogaster. When fed to flies, TSA caused lethality and delayed development at concentrations as low as 5 μM, had stronger effects on males than females, and acted synergistically with mutations in the gene encoding the RPD3 deacetylase to cause notched wings, but did not appear to affect a SINA signaling pathway that is normally repressed by the SIN3 corepressor. These findings suggest that deacetylated histones play an important role in normal developmental progression and establish parameters for genetic screens to dissect the role of deacetylases in this process. Received 14 June 2001; received after revision 31 July 2001; accepted 21 August 2001     

Molecular parasitology: progress towards the development of vaccines for malaria, filariasis, and schistosomiasis

Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages of Plasmodium and Schistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed.     

The genetic code in mitochondria and chloroplasts

The universal genetic code is used without changes in chloroplasts and in mitochondria of green plants. Non-plant mitochondria use codes that include changes from the universal code. Chloroplasts use 31 anticodons in translating the code; a number smaller than that used by bacteria, because chloroplasts have eliminated 10 CNN anticodons that are found in bacteria. Green plant mitochondria (mt) obtain some tRNAs from the cytosol, and genes for some other tRNAs have been acquired from chloroplast DNA. The code in non-plant mt differs from the universal code in the following usages found in various organisms: UGA for Trp, AUA for Met, AGR for Ser and stop, AAA for Asn, CUN for Thr, and possibly UAA for Tyr. CGN codons are not used by Torulopsis yeast mt. Non-plant mt, e.g. in vertebrates, may use a minimum of 22 anticodons for complete translation of mRNA sequences. The following possible causes are regarded as contributing to changes in the non-plant mt: directional mutation pressure, genomic economization, changes in charging specificity of tRNAs, loss of release factor RF2, changes in RF1, changes in anticodons, loss of lysidine-forming enzyme system, and disappearance of codons from coding sequences.     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

The binding of extra histone and protamine to deoxyribonucleoprotein

Résumé La déoxyribonucléoprotéine (DNP) du thymus de veau peut lier de l'histone supplémentaire en solution physiologique. La plupart de cette protéine est très faiblement liée et s'est degagée par HCl de 3,3 mM ou moins. On suggère ainsi que l'histone supplémentaire soit combinée aux groupes carboxyl des histones originales du DNP. Néanmoins, environ 10% de la protamine, ajouté pareillement au DNP, fut liée fortement ce qui suggère qu'elle peut atteindre les groupes phosphates libres sur l'ADN. La protamine apparemment n'a pas deplacée les histones lorsqu'elle fut liée au DNP.     

Extraction and analysis of histone protein from the roots of three plant species

Résumé Des essais réitérés ont montré aux auteurs que la protéine extraite des racines d'Allium cepa, deVicia faba et dePisum sativum est identifiable à l'histone. L'analyse de l'amine acide des hydrolysates des histones ne révèle pas de différences entre les trois espèces végétales citées et le thymus de veau. Dans les végétaux, cependant, le rapport lysine-arginine est plus élevé.

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The research was partially supported by the US Atomic Energy Commission under Contract AT(11-1)826.     

The extractibility of calf thymus histone fractions

Zusammenfassung Bei der Extraktion von Zellkernen mit Hilfe verdünnter Salzsäure ändert sich die Zusammensetzung einzelner Extrakte in Abhängigkeit von der Konzentration der benutzten Säure. Die Fraktion des Kalbsthymushistons, die an Arginin und Tyrosin reich ist, scheint an die Desoxyribonukleinsäure des Zellkernes fester gebunden zu sein als die zweite, an Tyrosin arme und an Lysin reiche Fraktion.     

基于主题建模和静态分析技术的软件代码功能性主题获取方法

近年来,基于主题建模技术的代码理解方法成为研究热点之一.该类方法期望利用主题建模技术从软件代码中挖掘功能性主题,进而利用功能性主题帮助开发人员理解软件功能及其代码实现.然而,从代码挖掘出的主题中,功能性主题与其他类型主题(如横切性主题)混杂在一起,需要人工识别功能性主题;由于现有工作大多仅提供主题关联的词等基本信息,导致识别及应用功能性主题的过程费时费力.针对以上问题,本文提出了一种基于主题建模和静态分析技术的软件代码功能性主题获取方法.该方法在利用一组启发式过滤规则对代码进行预处理的基础上,基于主题建模技术从代码中挖掘原始主题;进而,基于代码静态分析获得的代码间结构关系,提出了一种名为主题内聚度的技术从原始主题中自动识别功能性主题;最后,定位主题关联的代码片段,并利用代码及其注释为主题生成自然语言描述文本,进一步帮助开发人员理解主题所体现的软件功能及其代码实现细节.本文基于一组开源软件代码进行了方法评估,评估结果表明本文方法能够有效获取功能性主题及其关联信息,进而帮助开发人员更好地理解软件功能及其代码实现.     

Evolution of the genetic code, protein synthesis and nucleic acid replication

A better definition of the structural and thermodynamic determinants of the interaction of nucleic acids with proteins is shedding light on the origin of the genetic code, protein synthesis, and nucleic acid replication. This is also allowing to show a consistent biochemical framework for the appearance of these fundamental synthetic mechanisms. This article reviews recent significant developments in the field, and discusses an integrated model for a biochemically plausible evolution of these fundamental mechanisms of synthesis. This model is based on sequence-specific interactions between abiotically synthesized polynucleotides and polypeptides, and can account for a coordinate evolution of the genetic code, protein synthesis, and nucleic acid replication in living cells.     

The accuracy of aminoacylation--ensuring the fidelity of the genetic code

The fidelity of protein biosynthesis rests not only on the proper interaction of the messenger RNA codon with the anticodon of the tRNA, but also on the correct attachment of amino acids to their corresponding (cognate) transfer RNA (tRNA) species. This process is catalyzed by the aminoacyl-tRNA synthetases which discriminate with remarkable selectivity amongst many structurally similar tRNAs. The basis for this highly specific recognition of tRNA by these enzymes (also referred to as 'tRNA identity') is currently being elucidated by genetic, biochemical and biophysical techniques. At least two factors are important in determining the accuracy of aminoacylation: a) 'identity elements' in tRNA denote nucleotides in certain positions crucial for protein interactions determining specificity, and b) the occurrence in vivo of competition between synthetases for a particular tRNA which may have ambiguous identity.     

The molecular role of the Rothmund-Thomson-, RAPADILINO- and Baller-Gerold-gene product, RECQL4: recent progress

The RecQ family of DNA helicases is highly conserved throughout evolution and plays an important role in the maintenance of genomic stability in all organisms. Mutations in three of the five known family members in humans, BLM, WRN and RECQL4, give rise to disorders that are characterized by predisposition to cancer and premature aging, emphasizing the importance of studying the RecQ proteins and their cellular activities. Interestingly, three autosomal recessive disorders have been associated with mutations in the RECQL4 gene: Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes, thus making RECQL4 unique within the RecQ family of DNA helicases. To date, however, the molecular function of RECQL4 and the possible cellular pathways in which it is involved remain poorly understood. Here, we present an overview of recent findings in connection with RECQL4 and try to highlight different directions the field could head, helping to clarify the role of RECQL4 in preventing tumorigenesis and maintenance of genome integrity in humans. Received 31 October 2006; received after revision 4 January 2007; accepted 5 February 2007     

The Wilcoxon and related tests of significance

Résumé Une formule assez simple permet le calcul rapide des probabilités dans le test deWilcoxon et d'autres méthodes semblables. Sans fournir des résultats exacts, elle donne, dans les exemplaires choisis, des chiffres qui se rapprochent de la formule exacte deVan der Vaart, avec des erreurs inférieures à 1%.     

The adaptive significance of sexuality

Summary A theory of sexuality and polymorphism is proposed in which diversity at the molecular level is the adaptive response of multicellular organisms to the challenge of microparasites that have smaller genomes, shorter generation times and which can evolve more quickly than their hosts. The theory has implications for genetically homogenized crops and other cultivated plants as well as for immunology. A different function of sexuality is proposed for microorganisms that reproduce both asexually and sexually. Several possible experimental tests are discussed. Mathematical modelling techniques are outlined qualitatively and compared with game-theoretical methods which may be interpreted as simplifications of population dynamic and genetic equilibria. Some results about equilibria, stability and extinction in the population dynamics of polymorphic host-parasite populations are referenced.